Inhibition of semicarbazide-sensitive amine oxidase activity: possible functional consequences

Semicarbazide-Sensitive Amine Oxidases (SSAO) are ubiquitous enzymes whose physiological function(s) remain unclear. SSAO activity is high in vascular smooth muscle cells (VSMC). Aortas of weanling rats treated with SSAO inhibitors showed histopathological alterations of collagen and elastin with resultant pathophysiology suggesting a role for SSAO in extracellular matrix production and/or maintenance. To examine the relationship between SSAO, collagen, elastin, and aortic physiological function, VSMC were treated in vitro and weanling rats were treated in vivo with SSAO inhibitors (semicarbazide and MDL 72,145A-Marion Merrell Dow). Semicarbazide reduced elastin while MDL markedly increased elastin content in VSMC cultures. Elastin from MDL treated cultures appeared grossly abnormal. Aortic rings from SSAO-inhibited rats showed reduced tension development (suggesting reduced elasticity) and dilation of the distal thoracic aorta upon gross examination. Our data suggest a causal link between SSAO inhibition and altered aortic molecular composition with corresponding abnormal function.